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인간 대장암에서 AMPK/ACC 신호전달 경로를 통한 뷰티레이트에 의한 내성유도에 관한 연구
- Alternative Title
- Yoo, Hee Young
- Author(s)
- 유희영
- Alternative Author(s)
- Yoo, Hee Young
- Advisor
- 김소희
- Department
- 일반대학원 약학과
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2020-02
- Language
- eng
- Keyword
- AICAR; AMPK; butyrate; colon cancer; resistance
- Alternative Abstract
- Butyrate, a short-chain fatty acid produced by the colonic bacterial fermentation, inhibits cell growth in human colon cancer cells through the inhibition of histone deacetylases. However, chronic exposure to butyrate induces the resistance to butyrate in human colon cancer cells. The mechanism for the acquisition of resistance has not yet been fully understood. Butyrate-resistant (BR) cancer cells were developed by gradually increasing the butyrate concentration up to 1.6 mM for approximately 3 months in HCT116, HT29 and SW480 human colon cancer cells. The butyrate concentrations that inhibited cell growth by 50% (IC50) were increased by 11.8, 13.2 and 6.10-fold in HCT116, HT29 and SW480 BR cells, respectively, then their parental (PT) cells. Butyrate-resistance induced the autophagy through higher expression of Beclin-1 and LC3B. The expression of AMP-activated protein kinase (AMPK) was down-regulated in BR cells along with the activation of AKT and mTOR compared to respective PT cells. Decreased AMPK expression resulted in the expression of enzymes involved in fatty acid synthesis, such as acetyl-CoA carboxylase (ACC) and ATP citrate lyase (ACLY) in BR cells. Activation of AMPK by treating 5-Aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR, 1 mM) suppressed cell proliferation by inhibiting. Taken together, chronic butyrate exposure increased resistance to butyrate in the human colon cancer through down-regulation of AMPK/ACC signaling pathway, suggesting that AMPK could be a therapeutic target for BR colon cancers.
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Pharmacy > 3. Theses(Master)
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